Damiaan Denys

AmsterdamUMC · Psychiatry

Objective Selective serotonin reuptake inhibitors (SSRIs) are the first choice in pharmacotherapy for children and adolescents with obsessive-compulsive disorder (OCD). SSRI-trials for pediatric OCD have never been investigated using individual participant data (IPD), which is crucial for detecting patient-level effect modifiers. Here, we performed...

Objective Deep brain stimulation (DBS) targeting the ventral anterior limb of the internal capsule (vALIC) shows potential as treatment for treatment resistant depression (TRD). While DBS alters brain function, it is not yet known whether it also induces anatomical alterations. Here we investigated the long-term effects of vALIC DBS on brain struct...

Misophonia is a recently identified disorder of decreased sound tolerance that often originates in childhood. Currently, there is a lack of validated questionnaires for screening and assessing misophonia severity in children/adolescents. This paper presents an iterative validation process of two innovative (parallel child-/parent-reported) question...

Background An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. Arrhythmic disorders may play an important role herein, but the nature of the relationship between schizophrenia and arrhythmia is unclear. Aims To assess shared genetic liability and potential causal effects between schi...

Deep brain stimulation (DBS) reduces depressive symptom scores in many patients with treatment-resistant depression (TRD). However, it is unclear whether the observed improvement is similar across various symptom dimensions (e.g., anhedonia, anxiety, insomnia) or if some require additional clinical attention. Using a retrospective chart review, we...

Background The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID). Methods We analyzed individual participant data from short-term, double-blind, place...

A decoupling between confidence and action could relate to compulsive behaviour as seen in obsessive-compulsive disorder (OCD). The link between confidence and action in OCD has been investigated in clinical case-control studies and in the general population with discrepant findings. The generalizability of findings from highly-compulsive general p...

Deep brain stimulation (DBS) is a neurosurgical intervention for severe, treatment-refractory obsessive-compulsive disorder (OCD). Here, we conducted the first meta-analysis using individual participant outcome data, comparing DBS to sham-stimulation in randomized controlled trials (RCTs), and systematically evaluated adverse events and methodologi...

Deep brain stimulation (DBS) is a neurosurgical intervention for severe, treatment-refractory obsessive-compulsive disorder (OCD). Here, we conducted the first meta-analysis using individual participant outcome data, comparing DBS to sham-stimulation in randomized controlled trials (RCTs), and systematically evaluated adverse events and methodologi...

Background Little is known about the effect of ethnicity on drug treatment in patients with an acute manic episode. The aim of this study is to determine whether ethnicity moderates the response to drug treatment in patients with an acute manic episode, and whether this moderation is independent of potential confounders. Methods We analysed ten sh...

Deficits in cognitive flexibility are a frequent symptom of obsessive-compulsive disorder (OCD) and have been hypothesized to drive compulsive behavior. Sign- and goal-tracking behaviors are thought to be related to cognitive flexibility, yet have not been studied in this context. To investigate the relationship between sign- and goal-tracking beha...

Our essay starts from our first-person experience of visiting El Eco Experimental Museum in Mexico City. Over the course of our visit, El Eco became, what we will call an ‘intimate place’ in which we were able to explore personal thoughts, memories, and feelings. We go on to compare El Eco to Black Water (2021), a site-specific art installation by...

Obsessive-compulsive disorder (OCD) symptoms arise when a “natural” feeling of certainty is lost. OCD patients typically attempt to regain this feeling of certainty by means of overly conscious thinking, magical rituals, and repetitive behaviors. Ironically, these OCD symptoms might provide some relief in the short term but lead to a further loss o...

In this chapter, we focus on the experience of anxiety and attempt to link this to clinical neuroscience. Our central argument is that anxiety is a heterogeneous construct and that the different subjective experiences of anxiety may relate to different neurocircuitry. There are, for example, differences in the experience of anxiety that may reflect...

We draw on insights from ecological psychology, explorative architecture, and psychiatry to provide an analysis of basic trust in relation to urban places. We use the term basic trust to refer to the attitude of certainty we express when we act in skilled, often unreflective, habitual ways in the living environment. We will argue that the basic tru...

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 control...

Background Southeast Asia has the highest suicide mortality worldwide. To improve our knowledge on the effectiveness of interventions for suicidal ideation (SI) in individuals with depression in Indonesia, we conducted a secondary analysis of a randomised controlled trial. Objective We explored whether an internet-based behavioural activation (BA)...

Question We examined the effect of study characteristics, risk of bias and publication bias on the efficacy of pharmacotherapy in randomised controlled trials (RCTs) for obsessive-compulsive disorder (OCD). Study selection and analysis We conducted a systematic search of double-blinded, placebo-controlled, short-term RCTs with selective serotonerg...

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, w...

Background Neuroimaging studies suggest an association between apathy after deep brain stimulation (DBS) and stimulation of the ventral part of the subthalamic nucleus (STN) due to the associative fibers connected to the non-motor limbic circuits that are involved in emotion regulation and motivation. We have previously described three patients wit...

Background Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and compulsions. We previously showed that a virtual reality (VR) game can be used to provoke and measure anxiety and compulsions in patients with OCD. Here, we investigated whether this VR game activates brain regions associated with symptom provoc...

Initial treatment for obsessive-compulsive disorder (OCD) consists of pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) and/or psychological treatment with cognitive behavioral therapy (CBT). The assumption is that both treatments have different neural working mechanisms, but empirical evidence is lacking. We investigat...

Depression is associated with abnormal functioning of the reward circuitry. Several deep brain stimulation (DBS) targets for treatment-resistant depression (TRD) directly modulate white matter bundles of the reward circuitry. Here we investigated whether baseline reward processing in the brain is associated with ventral anterior limb of the interna...

Question We examined the effect of study characteristics, risk of bias and publication bias on efficacy of pharmacotherapy in randomized controlled trials (RCTs) for obsessive-compulsive disorder (OCD). Study selection and analysis We conducted a systematic search for double-blinded, placebo controlled short-term RCTs with selective serotonergic re...

Question Partial remission of major depressive disorder (MDD) is a debilitating and distressing clinical state related to chronicity, morbidity and relapse. Although one-third of patients remit partially, evidence for treatment efficacy is unclear. We provide an overview of treatment options and their efficacy. Study selection and analysis Embase,...

Deep brain stimulation (DBS) is a promising intervention for treatment-resistant depression (TRD). Effects on cognitive functioning are unclear since they have been studied in small samples. We aim to estimate the impact of DBS on cognitive functioning in TRD with a systematic review and meta-analyses. After systematically searching PubMed we inclu...

Background Individuals with serious mental illness have a markedly shorter life expectancy. A major contributor to premature death is cardiovascular disease (CVD). We investigated associations of (genetic liability for) depressive disorder, bipolar disorder and schizophrenia with a range of CVD traits and examined to what degree these were driven b...

Background This study aims: (1) To compare cognitive and psychiatric outcomes after bilateral awake versus asleep subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson’s disease (PD). (2) To explore the occurrence of psychiatric diagnoses, cognitive impairment and quality of life after surgery in our whole sample. (3) To vali...

Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in...

Background Anorexia nervosa (AN) is a severe and life-threatening psychiatric disorder. Initial studies on deep brain stimulation (DBS) in severe, treatment-refractory AN have shown clinical effects. However, the working mechanisms of DBS in AN remain largely unknown. Here, we used a task-based functional MRI approach to understand the pathophysiol...

Background Euthanasia and assisted suicide (EAS) for patients with psychiatric disorders occupies a prominent place in the public debate, but little is known about the psychiatric patients requesting and receiving EAS. Objective To compare the social demographic and psychiatric profile of the patients who make a request for EAS and those who recei...

Background An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. While arrhythmic disorders play an important role in this, the nature of the relation between schizophrenia and arrhythmia is not fully understood. Methods We leveraged summary-level data of large-scale genome-wide associ...

Deep brain stimulation (DBS) is being investigated as treatment for patients with refractory major depressive disorder (MDD). However, little is known about how DBS exerts its antidepressive effects.Here, we investigated whether ventral anterior limb of the internal capsule (vALIC) stimulation modulates a limbic network centered around the amygdala...

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in...

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant depression (TRD). However, the working mechanisms of vALIC DBS in TRD remain largely unexplored. As major depressive disorder has been associated with aberrant amygdala functioning, we investigated whether vA...

BACKGROUND Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and compulsions. We previously showed that a virtual reality (VR) game can be used to provoke and measure anxiety and compulsions in patients with OCD. Here, we investigated whether this VR game activates brain regions associated with symptom provoc...

Background: Little is known about the effect of ethnicity on the response to antipsychotic medication in patients with schizophrenia. Aims: To determine whether ethnicity moderates the response to antipsychotic medication in patients with schizophrenia, and whether this moderation is independent of confounders. Method: We analysed 18 short-ter...

Background: Misophonia is a recently identified disorder in which individuals experience intense, uncontrollable and disproportional irritation, anger or disgust when confronted with specific sounds or stimuli associated with these sounds. Prevalence rates in children and adolescents are currently still to be investigated. The reported average age...

Objective: Deep brain stimulation is a treatment option for patients with refractory obsessive-compulsive disorder. A new generation of stimulators hold promise for closed loop stimulation, with adaptive stimulation in response to biologic signals. Here we aimed to discover a suitable biomarker in the ventral striatum in patients with obsessive co...

Deep brain stimulation (DBS) is an established neuromodulatory intervention against otherwise treatment-refractory obsessive-compulsive disorder (OCD). Several DBS targets, all of which are part of brain networks connecting basal ganglia and prefrontal cortex, alleviate OCD symptoms. Stimulation of these targets is thought to unfold its therapeutic...

Introduction People with misophonia experience strong negative emotional responses to sounds and associated stimuli—mostly human produced—to an extent that it may cause impairment in social functioning. The exact nature of the disorder remains a matter of ongoing research and debate. Here, we investigated the genetic etiology of misophonia to under...

Objective: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD) yet neural markers of optimized stimulation parameters are largely unknown. We aimed to describe (sub-)cortical electrophysiological responses to acute DBS at various voltages in OCD. Methods: We explored how DBS doses between 3-5...

Background: The association between perceived ethnic discrimination (PED) and mental health conditions is well studied. However, less is known about the association between PED and suicidal ideation, or the role of positive psychosocial factors in this association. Aims: To examine the association between PED and suicidal ideation among ethnic m...

Background: Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is effective for refractory obsessive-compulsive disorder (OCD), but patients typically require high stimulation voltages and DBS comes with a risk for adverse events (AE). Objective: The aim of the present study was to advance DBS for OCD by op...

Background Patients suffering from major depressive disorder (MDD) regularly experience non-response to treatment for their depressive episode. Personalized clinical decision making could shorten depressive episodes and reduce patient suffering. Although no clinical tools are currently available, machine learning analysis of electroencephalography...

Deep brain stimulation (DBS) is a promising intervention for treatment-resistant depression (TRD). Effects on cognitive functioningare unclear since they have been studied in small samples. We aim to estimate the impact of DBS on cognitive functioning in TRDwith a systematic review and meta-analyses. After systematically searching PubMed we include...

Introduction: Deep brain stimulation (DBS) is an effective treatment for treatment-refractory obsessive-compulsive disorder (OCD) and is currently being studied in several other psychiatric disorders [2]. Although it’s established effect in the treatment of OCD [1] and promising preliminary findings in other psychiatric disorders patients eligible...

Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in...

Introduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of recurrence(s) over 2-10 years in patients with recurrent depression. Objective: The aim of the study was to examine the effectiveness of PCT over 20 years on t...

Background In Major Depressive Disorder (MDD), emotion- and motivation related symptoms may affect effort during neuropsychological testing. Performance Validity Tests (PVT's) are therefore essential, but are rarely mentioned in research on cognitive functioning in MDD. We aimed to assess the proportion of MDD patients with demonstrated valid perfo...

Objective To determine whether gender and menopausal status moderates the response to antipsychotic medication in patients with schizophrenia. Methods We analyzed data of 22 short-term placebo-controlled registration trials of antipsychotic medications, which included 5,231 patients with schizophrenia. We applied two-step individual patient data m...

Background: Patients with obsessive-compulsive disorder (OCD) experience an exacerbation of symptoms under psychological distress. The neurobiological underpinnings of this effect of stress remain elusive. Here, we induced psychological distress to explore its effect on neural reactivity of the salience network during a symptom provocation task....

Conscious perception is thought to depend on global amplification of sensory input. In recent years, the basal ganglia have been implicated in gating conscious access due to their consistent involvement in thalamocortical loops. However, much of the evidence implicating the basal ganglia in these processes in humans is correlational. The current st...